Exploring Hippocampal Vulnerability: Diminished Angiogenic Capacity in the Hippocampus Compared to the Cortex

BackgroundThe hippocampus is one of the first regions affected in various neurodegenerative diseases. In this study, investigated the vascular factors contributing to its susceptibility, aiming to elucidate the underlying vascular mechanisms. MethodUtilizing publicly available single-cell databases, we analyzed the differential expression of genes in blood-brain barrier (BBB)-associated cells within the hippocampus and compared them to those in the cortex. Those genes were further validated in mouse and ischemia rat models. ResultsWe identified differentially expressed genes (DEGs) in endothelial cells, pericytes, and astrocytes in the BBB. Subsequent gene ontology (GO) enrichment analysis and protein-protein interaction (PPI) network analysis identified key hub genes: Kdr, Fn1, Pecam1, Cd34, and Cd93, that related to angiogenesis. They differential expression was then experimentally verified using micro-vessels from mouse and rat brains: In the rat ischemia model, we observed up-regulation of angiogenesis-related genes, including Kdr, Cd34, and Cd93, in the microvasculature of both the hippocampus and cortex, with relatively lower expression in the hippocampus. ConclusionThese findings suggest that the hippocampus has a reduced angiogenic capacity compared to the cortex, which may contribute to its increased vulnerability to neurological disorders.